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Biological Chemistry

Imaging Enzyme Replacement Therapy

PET imaging is used for the first time to monitor therapeutic enzyme distribution and lifetime

by Stuart A. Borman
June 7, 2010 | A version of this story appeared in Volume 88, Issue 23

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Credit: Stephen Withers
<em>This PET image shows organ uptake of an 
18F-labeled enzyme in mice.</em>
Credit: Stephen Withers
<em>This PET image shows organ uptake of an 
18F-labeled enzyme in mice.</em>

Positron emission tomography (PET) imaging has been used for the first time to monitor enzyme replacement therapy (ERT), an advance that could lead to more accurate dosages for patients (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1003247107). Direct enzyme replacement is used to treat Gaucher disease and other rare lysosomal storage diseases in which cell lysosomes fail to digest and recycle biomolecules properly owing to mutations in genes for specific enzymes. ERT restores normal enzyme to patients, but there are unanswered questions about optimal dosing, which organs an enzyme traffics to in the body, and how long the enzyme lasts. Stephen G. Withers of the University of British Columbia, Vancouver, and coworkers covalently labeled the active site of the enzyme used to treat Gaucher disease with 18F-glucose and injected it into mice. The team then used PET imaging to monitor the enzyme’s distribution and longevity. The technique is “a powerful research tool with an immediate clinical application to Gaucher disease and a clear path for application to other ERTs,” the researchers write.

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